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  4. Eradication of specific donor-dependent variations of mesenchymal stem cells in immunomodulation to enhance therapeutic values

Eradication of specific donor-dependent variations of mesenchymal stem cells in immunomodulation to enhance therapeutic values

Cell Death & Disease, 2021 · DOI: https://doi.org/10.1038/s41419-021-03644-5 · Published: April 29, 2021

Regenerative MedicineImmunology

Simple Explanation

Mesenchymal stem cells (MSCs) are widely used in clinical trials because they can differentiate into various cell types, secrete regenerative factors, and modulate immune functions. This study found that MSCs from different donors vary in their ability to proliferate and modulate the immune system, which may explain inconsistent clinical results. The study identified that IFN-γ and NF-κB signaling pathways are linked to the immune modulatory function of MSCs. Activating these pathways with IFN-γ and TNF-α can eliminate donor-dependent variations. Pre-selecting or pre-treating MSCs to remove variations in a way specific to the disease being treated is necessary to ensure the best clinical results. This study offers new insights for controlling the quality of MSCs from different donors when treating inflammation or autoimmune diseases.

Study Duration
Not specified
Participants
32 human umbilical-cord-derived MSC donors
Evidence Level
Not specified

Key Findings

  • 1
    Human umbilical cord-derived MSCs from 32 donors showed donor-dependent variations in proliferation and immune modulation capabilities.
  • 2
    IFN-γ and NF-κB signaling are positively correlated with the immune modulatory function of huMSCs; stimulation with IFN-γ and TNF-α can eliminate donor-dependent variations in immunomodulation.
  • 3
    Pretreatment with IFN-γ and TNF-α enhances immunomodulation but suppresses proliferation of huMSCs.

Research Summary

This study analyzed human umbilical-cord-derived MSCs from 32 donors and found donor-dependent variations in cell proliferation and immune modulatory functions, potentially explaining inconsistent clinical efficacies of MSCs. Transcriptomic analyses revealed that IFN-γ and NF-κB signaling were positively associated with immune modulatory function; activating these pathways eradicated donor-dependent variations. The study suggests pre-selection or pre-treatment of MSCs to eradicate variations in a disease-specific manner is necessary to ensure clinical efficacies, providing novel insights into the quality control of MSCs for treating inflammation-related conditions.

Practical Implications

Quality Control in MSC Therapies

Highlights the importance of quality control in MSC-based therapies, suggesting that not all MSCs are equal and preselection is key to effective clinical outcomes.

Personalized MSC Treatment

Emphasizes the need for disease-treatment-specific assays to address donor-dependent variations and tailor MSC normalization methods for different clinical applications.

Optimizing Immunomodulation

Suggests pretreatment with inflammatory factors like IFN-γ and TNF-α to enhance the immunomodulatory function of MSCs and eradicate donor-dependent variations, while acknowledging potential impacts on cell proliferation.

Study Limitations

  • 1
    The study focuses on umbilical cord-derived MSCs, and findings may not be generalizable to MSCs from other tissue sources.
  • 2
    The study identifies IFN-γ and NF-κB signaling as key factors, but other pathways may also contribute to donor-dependent variations.
  • 3
    The long-term effects of IFN-γ and TNF-α pretreatment on MSCs and their therapeutic efficacy require further investigation.

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